Melanocytes are deficient in repair of oxidative DNA damage and UV-induced photoproducts

• DOI: 10.1073/pnas.1005244107
• Publication Date: 2010-06-22T02:44:55Z
• Authors: Hsiang-Tsui Wang; Bongkun Choi; Moon-shong Tang
• Keywords: Melanins; 0301 basic medicine; 0303 health sciences; DNA Repair; Dose-Response Relationship, Drug; Ultraviolet Rays; Deoxyguanosine; Hydrogen Peroxide; Fibroblasts; Oxidants; Oxidative Stress; 03 medical and health sciences; DNA-Formamidopyrimidine Glycosylase; 8-Hydroxy-2'-Deoxyguanosine; Humans; Melanocytes; Cells, Cultured; DNA Damage; Skin

Melanomas occur mainly in sunlight-exposed skin. Xeroderma pigmentosum (XP) patients have 1,000-fold higher incidence of melanoma, suggesting that sunlight-induced “bulky” photoproducts are responsible for melanomagenesis. Sunlight induces a high level reactive oxygen species melanocytes (MCs); oxidative DNA damage (ODD) may thus also contribute to melanomagenesis, and XP gene products participate the repair ODD. We examined effects melanin on UVA (320–400 nm) irradiation-induced ODD UV capacity MC cells UV-induced photoproducts. Our findings indicate irradiation significantly amount formamidopyrimidine glycosylase-sensitive MCs than normal human skin fibroblasts (NHSFs). In contrast, an insignificant UvrABC-sensitive sites either these two types cells. found that, compared NHSFs, reduced photoproducts; H 2 O modified- UVC-irradiated DNAs induce mutation frequency NHSFs; and, complementation group A (XPA), C, G deficient XPA NHSFs. These results suggest that: ( i ) sensitizes induction but not bulky ii susceptibility UVA-induced carcinogenesis; iii contributes melanoma patients.